IL-2 requirement for human plasma cell generation: coupling differentiation and proliferation by enhancing MAPK-ERK signaling.

Simon Le Gallou 1, 2 Gersende Caron 1, 2, 3 Céline Delaloy 1, 2, 3 Delphine Rossille 3, 4 Karin Tarte 1 Thierry Fest 1, *
* Auteur correspondant
1 MiCa - Microenvironnement et cancer
2 Etablissement Français du Sang Bretagne
3 Pôle Cellules & Tissus
4 Modélisation Conceptuelle des Connaissances Biomédicales
Abstract : Mature B cell differentiation involves a well-established transcription factor cascade. However, the temporal dynamics of cell signaling pathways regulating transcription factor network and coordinating cell proliferation and differentiation remain poorly defined. To gain insight into the molecular processes and extrinsic cues required for B cell differentiation, we set up a controlled primary culture system to differentiate human naive B cells into plasma cells (PCs). We identified T cell-produced IL-2 to be critically involved in ERK1/2-triggered PC differentiation. IL-2 drove activated B cell differentiation toward PC independently of its proliferation and survival functions. Indeed, IL-2 potentiated ERK activation and subsequent BACH2 and IRF8 downregulation, sustaining BLIMP1 expression, the master regulator for PC differentiation. Inhibition of the MAPK-ERK pathway, unlike STAT5 signaling, impaired IL-2-induced PC differentiation and rescued the expression profile of BACH2 and IRF8. These results identify IL-2 as a crucial early input in mature B cell fate commitment.
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Article dans une revue
Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2012, 189 (1), pp.161-73. 〈10.4049/jimmunol.1200301〉
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http://www.hal.inserm.fr/inserm-00869090
Contributeur : Morgane Le Corre <>
Soumis le : mercredi 2 octobre 2013 - 14:41:16
Dernière modification le : mercredi 16 mai 2018 - 11:23:27

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U917 | BIOSIT | UR1-UFR-SVE | MICMAC | UNIV-RENNES

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Simon Le Gallou, Gersende Caron, Céline Delaloy, Delphine Rossille, Karin Tarte, et al.. IL-2 requirement for human plasma cell generation: coupling differentiation and proliferation by enhancing MAPK-ERK signaling.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2012, 189 (1), pp.161-73. 〈10.4049/jimmunol.1200301〉. 〈inserm-00869090〉

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